| 1. |
- Johansson, Dongni, 1988, et al.
(författare)
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Individualization of levodopa treatment using a microtablet dispenser and ambulatory accelerometry
- 2018
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Ingår i: CNS Neuroscience & Therapeutics. - : Wiley. - 1755-5930 .- 1755-5949. ; 24:5, s. 439-447
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This 4-week open-label observational study describes the effect of introducing a microtablet dose dispenser and adjusting doses based on objective free-living motor symptom monitoring in individuals with Parkinson's disease (PD). Methods: Twenty-eight outpatients with PD on stable levodopa treatment with dose intervals of ≤4 hour had their daytime doses of levodopa replaced with levodopa/carbidopa microtablets, 5/1.25 mg (LC-5) delivered from a dose dispenser device with programmable reminders. After 2 weeks, doses were adjusted based on ambulatory accelerometry and clinical monitoring. Results: Twenty-four participants completed the study per protocol. The daily levodopa dose was increased by 15% (112 mg, P < 0.001) from period 1 to 2, and the dose interval was reduced by 12% (22 minutes, P = 0.003). The treatment adherence to LC-5 was high in both periods. The MDS-UPDRS parts II and III, disease-specific quality of life (PDQ-8), wearing-off symptoms (WOQ-19), and nonmotor symptoms (NMS Quest) improved after dose titration, but the generic quality-of-life measure EQ-5D-5L did not. Blinded expert evaluation of accelerometry results demonstrated improvement in 60% of subjects and worsening in 25%. Conclusions: The introduction of a levodopa microtablet dispenser and accelerometry aided dose adjustments improve PD symptoms and quality of life in the short term.
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| 2. |
- Bergquist, Filip, 1970, et al.
(författare)
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Motor Efficacy of Subcutaneous DIZ102, Intravenous DIZ101 or Intestinal Levodopa/Carbidopa Infusion
- 2024
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Ingår i: MOVEMENT DISORDERS CLINICAL PRACTICE. - : WILEY. - 2330-1619.
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa. Objectives: To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms. Methods: Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist-worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph). Results: There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG. Conclusion: Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.
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| 3. |
- Bergquist, Filip, et al.
(författare)
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Parkinsons sjukdom – heterogen och komplex i sitt kliniska uttryck - Individuella kombinationer av symtom som ändrar sig över tid kräver behandlingsjusteringar och anpassningar
- 2020
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Ingår i: Läkartidningen. - 0023-7205. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinson's disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinson's disease.
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| 4. |
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| 5. |
- Bergquist, Filip, et al.
(författare)
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Parkinsons sjukdom [Parkinsons disease] : heterogen och komplex i sitt kliniska uttryck [heterogeneous and complex in its clinical presentation]
- 2020
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Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Parkinsons disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinsons disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinsons disease.
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| 6. |
- Bergquist, Filip, et al.
(författare)
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Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
- 2022
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Ingår i: Neurology. - : Lippincott, Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 99:10, s. E965-E976
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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| 7. |
- Busk, Karin, et al.
(författare)
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Long-term efficacy and safety with continuous dopaminergic stimulation pump treatments in Parkinson's disease
- 2011
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Ingår i: European Neurological Review. - 1758-3837. ; 6:3, s. 156-160
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Tidskriftsartikel (refereegranskat)abstract
- Continuous dopaminergic stimulation (CDS) is important for symptom control in advanced stages of Parkinson’s disease (PD). The most efficacious approaches are pump treatments with dopaminergic drugs: subcutaneous infusion of the dopamine receptor agonist apomorphine and intestinal infusion of levodopa/carbidopa gel. Both methods decrease motor fluctuations in long-term follow-ups, including parkinsonian and dyskinetic states, when compared to conventional optimised oral therapy. Also non-motor symptoms may be improved. Adverse drug reactions are usually less pronounced although high levodopa doses, which are common with levodopa/carbidopa infusion, may cause hyperhomocysteinaemia and cobalamin deficiency. Technical complications are specific for each infusion strategy. Formation of subcutaneous nodules is the most common problem with apomorphine infusion. Dislocation of the intestinal tube is the most common problem with levodopa/carbidopa infusion. Both pump treatments may be used for 24-hour infusion in selected patients. The long-term experience is reviewed. To conclude, CDS pump treatments may be successfully used for several years in advanced PD.
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| 8. |
- Gretarsdottir, Helga Maria, et al.
(författare)
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Personalized Medicine Approach in Treating Parkinson's Disease, Using Oral Administration of Levodopa/Carbidopa Microtablets in Clinical Practice
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The most effective symptomatic treatment in Parkinson's disease (PD) is levodopa in standard doses. However, as the disease progresses, there may be a need for a more personalized approach and fine tuning, in accordance with the patients' needs. This study aims to evaluate the individual experience of levodopa/carbidopa 5/1.25 mg microtablets (LC-5) in clinical practice with respect to efficacy, tolerability, and usability. The method used was as follows: patients answered a questionnaire concerning the effect and usability of LC-5, and their medical records were reviewed. Regarding results, thirty-five survey responses were obtained, and 29 patients' medical records were reviewed. The LC-5 dose dispenser usability was generally rated positively and facilitated medication adherence. The majority (85%) of patients reported symptom improvement while using LC-5, compared with previous standard treatments. These results suggest that LC-5 therapy is generally well-tolerated, with favorable patient-reported efficacy and user friendliness, as well as the possibility for an individualized, fine-tuned PD treatment. Further studies with a prospective design and larger study population are needed to confirm the results.
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| 9. |
- Johansson, Anders, et al.
(författare)
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Continuous delivery of energy or L-dopa: Identifying advantages and limitations of DBS and levodopa-carbidopa intestinal gel in ansence of head-to-head comparisons
- 2012
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Ingår i: Basal Ganglia. - : Elsevier BV. - 2210-5336. ; 2:4, s. 221-226
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) and levodopa–carbidopa intestinal gel (LCIG) are invasive, efficacious treatments for advanced Parkinson’s disease, but so far head-to-head comparisons are scarce. Although their indications and improvements in motor outcome and quality of life may be broadly similar, these treatment modalities have different modes of action and side effect profiles. This article summarizes a presentation at the 2nd International Conference on Knowledge Gaps in Parkinson’s Disease and other Movement Disorders in Feburary 2012. An overview of the existing evidence for efficacy and adverse events of LCIG and DBS in short- and long-term is provided. Examples of factors at present affecting choice of treatment are given. The obvious knowledge gap is the need to better identify the appropriate time and place to operate patients with Parkinson’s disease. There are major difficulties facing us when trying to resolve this issue. We argue for a registry of patients exposed to these very efficacious, but expensive and potentially harmful, symptomatic treatments.
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